Nanoparticles comprising aminoacyl tRNA synthetase and anticancer composition comprising same

Abstract

The present invention relates to nanoparticles comprising aminoacyl tRNA synthetase and an anticancer composition comprising the same and, specifically, to nanoparticles which comprise glycyl-tRNA synthetase (GRS), leucyl-tRNA synthetase (LRS), and isoleucyl-tRNA synthetase (IRS), and have anticancer or immunostimulating activity; a pharmaceutical composition for preventing or treating cancer, comprising the nanoparticles as an active ingredient; a composition for immunostimulation; and a method for preparing the nanoparticles.

The invention claimed is: 
     
       1. A method for treating cancer or enhancing immune function in a subject, the method comprising administering an effective amount of nanoparticles to a subject in need of treating cancer or enhancing immune function,
 wherein the nanoparticles comprise glycyl-tRNA synthetase (GRS), leucyl-tRNA synthetase (LRS), and isoleucyl-tRNA synthetase (IRS), 
 wherein the GRS comprises an amino acid sequence of SEQ ID NO: 1 and the 390 th  amino acid cysteine in the amino acid sequence of SEQ ID NO: 1 is palmitoylated. 
 
     
     
       2. The method of  claim 1 , wherein the cancer is at least one selected from the group consisting of breast cancer, colorectal cancer, lung cancer, small cell lung cancer, gastric cancer, liver cancer, blood cancer, bone cancer, pancreatic cancer, skin cancer, head or neck cancer, cutaneous or intraocular melanoma, eye tumor, peritoneal cancer, uterine cancer, ovarian cancer, rectal cancer, anal cancer, colon cancer, fallopian tube carcinoma, endometrial carcinoma, cervical cancer, vaginal cancer, vulvar carcinoma, Hodgkin's disease, esophageal cancer, small intestine cancer, endocrine cancer, thyroid cancer, parathyroid carcinoma, adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer, prostate cancer, testicular cancer, oral cancer, gallbladder cancer, cholangiocarcinoma, chronic or acute leukemia, lymphocyte lymphoma, bladder cancer, kidney cancer, ureteral cancer, renal cell carcinoma, renal pelvic carcinoma, CNS tumor, primary CNS lymphoma, spinal cord tumor, brain stem glioma, and pituitary adenoma. 
     
     
       3. The method of  claim 1 , wherein the LRS comprises an amino acid sequence of SEQ ID NO: 2, and the IRS comprises an amino acid sequence of SEQ ID NO: 3. 
     
     
       4. The method of  claim 1 , wherein the nanoparticles are prepared by a method comprising:
 (a) inducing an artificial apoptotic stress to cells; 
 (b) collecting nanoparticles secreted from the cells in step (a); and 
 (c) determining whether the collected nanoparticles comprise glycyl-tRNA synthetase (GRS), leucyl-tRNA synthetase (LRS), and isoleucyl-tRNA synthetase (IRS), wherein the GRS comprises an amino acid sequence represented by SEQ ID NO: 1 and the 390 th  amino acid cysteine in the amino acid sequence of SEQ ID NO: 1 is palmitoylated. 
 
     
     
       5. The method of  claim 4 , wherein the apoptotic stress is at least one selected from the group consisting of oxygen deficiency, glucose starvation, Fas ligand treatment, tumor necrosis factor-α (TNF-α) treatment, TNF-β treatment, TNF-related apoptosis inducing ligand (TRAIL) treatment, perforin treatment, Bax protein treatment, Bak protein treatment, and adriamycin treatment. 
     
     
       6. The method of  claim 4 , wherein the cells in step (a) are immune cells. 
     
     
       7. The method of  claim 1 , wherein the nanoparticles are prepared by a method comprising:
 (a) co-culturing non-cancer cells and cancer cells; 
 (b) collecting nanoparticles secreted from the non-cancer cells in step (a); and 
 (c) determining whether the collected nanoparticles comprise glycyl-tRNA synthetase (GRS), leucyl-tRNA synthetase (LRS), and isoleucyl-tRNA synthetase (IRS), wherein the GRS comprises an amino acid sequence represented by SEQ ID NO: 1 and the 390 th  amino acid cysteine in the amino acid sequence of SEQ ID NO: 1 is palmitoylated. 
 
     
     
       8. The method of  claim 7 , the method further comprises (d) differentiating exosomes from the nanoparticles collected in step (b). 
     
     
       9. The method of  claim 8 , wherein the exosomes comprise at least one marker selected from the group consisting of syntenin-1, CD9, CD63, and CD81. 
     
     
       10. The method of  claim 7 , wherein the nanoparticles further comprise vimentin and insulin-like growth factor 2 receptor (IGF2R). 
     
     
       11. The method of  claim 7 , wherein the non-cancer cells in step (a) are immune cells.